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PVSRIPO for Patients With Unresectable Melanoma

28. juni 2022 oppdatert av: Istari Oncology, Inc.

A Phase I Trial of PVSRIPO for Patients With Unresectable Melanoma

This study is a Phase I study of oncolytic polio/rhinovirus recombinant (PVSRIPO) to primarily characterize the safety and tolerability of PVSRIPO in patients with AJCC Stage IIIB, IIIC, or IV melanoma in a modified 3+3 phase 1 trial design. Lesion biopsies and blood samples will be obtained pre- and post-injection throughout the study for routine histology/molecular genetic testing and immunologic analysis, respectively. Exploratory objectives include describing the response rates of PVSRIPO-injected versus non-injected lesion(s), the number of CD8 positive T cells present in the tumor biopsies before and after injection of PVSRIPO, and after PVSRIPO administration: the pathologic response in tumor biopsies, changes in the tumor microenvironment, and how systemic immune cell populations may change.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

The Primary Objective of the study is to determine the safety profile of PVSRIPO in Stage IIIB, IIIC, and IV recurrent melanoma patients as determined by DLTs by cohort, as well as in those retreated with PVSRIPO, when PVSRIPO is injected intralesionally into 1 to 3 or more cutaneous or subcutaneous lesions. As planned, up to 18 patients may be treated with PVSRIPO.

Biopsy material will be obtained from tumor tissue prior to and following virus administration, which may be subjected to routine histology along with molecular genetic testing and evaluation of pathological response. Whole blood for immunologic analyses will also be collected throughout the study period.

Routine study visits will occur through Day 126. Thereafter, visits will occur every 2-3 months for up to 2 years for subjects who do not progress. For patients with progressive disease, chart review only will occur every 3 months starting at the time of progression.

Patients who previously participated in Cohorts 0 through 3, who in the opinion of the investigator, may benefit from continued PVSRIPO administration, may be eligible to receive additional injections.

Studietype

Intervensjonell

Registrering (Faktiske)

12

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

    • North Carolina
      • Durham, North Carolina, Forente stater, 27710
        • Duke University Medical Center

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Undergone prior vaccination against PV and received a boost immunization with trivalent IPOL® (Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to administration of PVSRIPO (within 6 months of PVSRIPO retreatment).

    a. Note: Patients who are unsure of their prior vaccination status/who have not been vaccinated must provide proof of vaccination and/or evidence of anti-PV immunity prior to enrollment, as applicable.

  2. The patient must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) at least 1 week prior to administration of the study agent.
  3. Patient must have histologically proven unresectable, recurrent, melanoma, stage IIIB, IIIC, or stage IV (AJCC staging must be documented in patient's medical record, as determined by CT of the chest, abdomen and pelvis, and/or whole body PET scan, and MRI of the brain within 4 weeks prior to administration of study drug).
  4. Patients with BRAF mutations, must have failed at least 2 lines of therapy, specifically one BRAF targeted therapy and at least one anti-PD-1 based therapy. For BRAF wild type, patients must have failed at least one anti-PD-1 based therapy.
  5. Patient must be ≥ 18 years of age.
  6. Patient must have an ECOG/Zubrod status of 0-1.
  7. Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the irRC criteria.
  8. At least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion ≥ 10 mm in longest diameter or, multiple injectable melanoma lesions which in aggregate have a longest diameter of ≥ 10 mm (Cohorts 0 and possibly 1). For cohorts where 2 or 3 injections are planned (Cohorts 1 and 2), the patient must have at least 2 injectable melanoma lesions (when 2 doses are planned) or ≥3 injectable melanoma lesions when at least 3 doses are planned in different lesions (Cohorts 2 through 4).

    a. Note: PVSRIPO retreatment requires ≥2 lesions amenable to injection.

  9. At least one measurable lesion that will not be injected.
  10. Serum lactate dehydrogenase (LDH) levels less than 1.5 x upper limit of normal (ULN).
  11. Patient must have adequate bone marrow, liver and renal function as assessed by the following:

    1. Hemoglobin > 9.0 g/dl
    2. White blood count (WBC) of > 2000 m3
    3. Absolute neutrophil count (ANC) > 1,000/mm3
    4. Platelet count > 75,000/mm3
    5. Total bilirubin < 2.0 x ULN
    6. ALT and AST < 2.5 x the ULN

Exclusion Criteria:

  1. Females who are pregnant or breast-feeding.
  2. Adults of reproductive potential not employing an effective method of birth control.
  3. Patients with severe, active co-morbidity, defined as follows:

    1. Patients with an active infection requiring treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C).
    2. Patients with impaired cardiac function or clinically significant cardiac disease, such as congestive heart failure requiring treatment (New York Heart Association Class ≥ 2), uncontrolled hypertension or clinically significant arrhythmia; QTcF > 470 msec on ECG if performed or congenital long QT syndrome; acute myocardial infarction or unstable angina pectoris < 3 months prior to study.
    3. Patients with known lung (FEV1 < 50%) disease or uncontrolled diabetes mellitus (HgbA1c>7).
    4. Patients with albumin allergy.
    5. Autoimmune disease: History of or current active autoimmune diseases, [e.g. including but not limited to inflammatory bowel diseases [IBD], rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome)]. Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary.
    6. Known immunosuppressive disease, human immunodeficiency virus (HIV) infection, or chronic Hepatitis B or C.
  4. Patients with a previous history of neurological complications due to PV infection.
  5. Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used. Toxicities must have resolved to CTCAE grade 1 or less with the following exceptions (alopecia, fatigue, vitiligo).
  6. Patients with undetectable anti-tetanus toxoid IgG.
  7. Patients with known history of agammaglobulinemia.
  8. Patients on greater than 10 mg per day of prednisone within the 2 weeks prior to admission for PVSRIPO injection.
  9. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups).
  10. Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin.
  11. Clinically active cerebral or bone metastases.
  12. Greater than 3 visceral metastases (this does not include nodal metastases associated with visceral organs).
  13. Prior allogeneic stem cell transplantation.
  14. Concomitant therapy with any of the following: IL-2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). However, during the course of the study, use of corticosteroids is allowed if used for treating irAEs, adrenal insufficiencies, or if administered at doses of prednisone 10 mg daily or equivalent.
  15. Active clinically serious infection > CTCAE Grade 2.
  16. Antineoplastic therapy, radiotherapy, or any other investigational drug within 15 days prior to first study drug administration.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Sekvensiell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Cohort 0 (PVSRIPO)
A single dose of PVSRIPO into a single lesion.
Intralesional injection of PVSRIPO.
Eksperimentell: Cohort 1 (PVSRIPO)
A single dose of PVSRIPO into 2 different lesions, 21 days apart, when applicable per dose escalation guidelines.
Intralesional injection of PVSRIPO.
Eksperimentell: Cohort 2 (PVSRIPO)
A single dose of PVSRIPO into 3 different lesions, 21 days apart, when applicable per dose escalation guidelines.
Intralesional injection of PVSRIPO.
Eksperimentell: Cohort 3 (PVSRIPO)
A single dose of PVSRIPO into 3 different lesions, 21 days apart, when applicable per dose escalation guidelines.
Intralesional injection of PVSRIPO.
Eksperimentell: Cohort 4 (PVSRIPO)
A single dose of PVSRIPO into a single lesion, followed by PVSRIPO injected into up to 6 lesions at Day 10 and every 21 days thereafter.
Intralesional injection of PVSRIPO.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Proportion of patients with DLTs by cohort
Tidsramme: 24 months
To characterize the safety and tolerability of PVSRIPO in AJCC Stage IIIB, IIIC, or IV melanoma.
24 months

Andre resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Response rates via measurement of cutaneous lesions every 3 weeks
Tidsramme: 24 months
To describe the response rates via lesion size of PVSRIPO-injected versus non-injected lesion(s).
24 months
Number of CD8 positive T cells by IHC on pre treatment and post treatment biopsy (Cohorts 0-3 only)
Tidsramme: 4.1 months
To describe the number of CD8 positive T cells present in the tumor biopsies before and after injection of PVSRIPO.
4.1 months
The change in tumor pathology from baseline to after PVSRIPO injection
Tidsramme: 4.1 months
Determine the pathologic response in tumor biopsies after PVSRIPO by confirming presence or absence of viable tumor cells.
4.1 months
The detection of viral replication in injected versus non injected lesions (Cohorts 0-3 only)
Tidsramme: 4.1 months
Determine viral replication via a number of methods (e.g., qRT-PCR, ICH).
4.1 months
The change in inflammatory cells and markers after PVSRIPO in injected versus non injected lesions (Cohorts 0-3 only)
Tidsramme: 4.1 months
Determine changes in the tumor microenvironment from biopsies after PVSRIPO; includes but not limited to examination of CD8, PVR (CD155), PD-L1, CD4, FoxPE, and PD-1.
4.1 months
Change relative to baseline in type and/or function of T cells via flow cytometry (Cohorts 0-3 only)
Tidsramme: 24 months
Describe how systemic immune cell populations may change after treatment with PVSRIPO.
24 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Samarbeidspartnere

Etterforskere

  • Hovedetterforsker: Georgia Beasley, MD, Duke University

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

26. november 2018

Primær fullføring (Faktiske)

23. mars 2021

Studiet fullført (Faktiske)

23. mars 2021

Datoer for studieregistrering

Først innsendt

5. oktober 2018

Først innsendt som oppfylte QC-kriteriene

17. oktober 2018

Først lagt ut (Faktiske)

19. oktober 2018

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

30. juni 2022

Siste oppdatering sendt inn som oppfylte QC-kriteriene

28. juni 2022

Sist bekreftet

1. juni 2022

Mer informasjon

Begreper knyttet til denne studien

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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